Thromboembolic events in severe postpartum hemorrhage treated with recombinant activated factor VII: a systematic literature review and meta-analysis

Postpartum hemorrhage (PPH) is an obstetric complication with high associated morbidity. Recombinant activated factor VII (rFVIIa) is used to treat severe PPH when uterotonics fail to stop bleeding. However, data on the safety of rFVIIa treatment of severe PPH from adequately powered trials are lacking. We systematically reviewed published data on the incidence of thromboembolic events (TEs) in women with PPH treated or not treated with rFVIIa (PROSPERO CRD42022360736). Databases (Embase, MEDLINE, BIOSIS, Current Contents, and the Cochrane Library) were searched for peer-reviewed publications published between January 1996 and August 2022 and conference abstracts published between January 2017 and August 2022 using search terms related to thromboembolism or infarction and PPH. Data were extracted from all publications reporting on a general population of women with PPH with information on TEs. Descriptive summary statistics and the estimated proportion of TEs were analyzed using a generalized linear mixed model based on the binomial distribution. Quality assessments were based on the checklist by Downs and Black. From 1637 potentially eligible studies, 55 publications were included reporting on 611 women treated and 32,488 women not treated with rFVIIa. The global estimated proportion of TEs was 1.82% (prediction interval [PI], 0.30-10.23) and 0.72% (PI, 0.03-16.47) in women with severe PPH treated and those not treated with rFVIIa, respectively. The estimated proportions of TEs were similarly small, with wide and largely overlapping PIs. Additional well-designed trials are needed to improve understanding of TE incidence in PPH.